Diabetes-related changes in L-tryptophan-induced release of striatal biogenic amines

In vivo voltammetry was used to measure the synaptic release of rat striatal dopamine and serotonin after the administration of the amino acid L-tryptophan to streptozocin-induced diabetic rats. Dopamine and serotonin release from rat striatum was studied at a short-term or acute (3-day) interval and a long-term or chronic (3- to 7-wk) interval after the induction of diabetes. The study was also done in age-, sex-, and food-matched controls. The findings show that L-tryptophan decreased dopamine release from rat striatum in nondiabetic rats. The decreased striatal dopamine release, after L-tryptophan administration, was exacerbated in acutely diabetic rats and further exacerbated in chronically diabetic rats. By contrast, rat striatal serotonin release predictably increased after L-tryptophan injection in nondiabetic rats. A further increased striatal serotonin release was seen in acutely diabetic rats. Chronically diabetic rats, however, responded to L-tryptophan with a dramatic and significant decrease in striatal serotonin release. The results show that in acutely diabetic and normal rats, L-tryptophan administration reduced striatal dopamine and increased striatal serotonin release, whereas in chronically diabetic rats, the release of both biogenic amines was decreased. The findings indicate that the progression of diabetes is associated with an impaired ability to release primary neurotransmitter biogenic amines.     

Dynamic computed tomography of the head and neck: differential diagnostic value

A retrospective review of the dynamic CT studies performed in our institution on head and neck lesions, excluding the brain, was carried out. Five basic types of density vs. time curves were obtained. Dynamic CT scanning is valuable in the differential diagnosis, management, and followup of such cases; its usefulness as an imaging modality in diagnosis and followup of hemangiomas is stressed.     

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation

Background: Eosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation. Objective: Our purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus. Methods: Family members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines. Results: Three short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients’ plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption. Conclusion: Eosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking. (J Am Acad Dermatol 1998;38:919-28.)     

A Clinical Guide to Combination Lipid-Lowering Therapy

Purpose of Review

We provide an overview of our current understanding of combination lipid-lowering therapies intended for dyslipidemia treatment and cardiovascular disease prevention. First, we analyze recent statin and non-statin combination therapy guidelines and clinical studies since the publication of 2013 American College of Cardiology Cholesterol Guidelines. Second, we examine the clinical utility of non-statin agents alone and in combination in terms of LDL-C lowering and ASCVD risk reduction.

Recent Findings

Medical societies, including the American College of Cardiology (ACC), National Lipid Association (NLA), and American Association of Clinical Endocrinologists (AACE), have released guidelines to address the appropriate use of non-statin therapies. The guidelines incorporated new evidence, including the IMPROVE-IT and FOURIER clinical trials, which demonstrate that the combination of statin therapy with other non-statin agents such as ezetimibe and PCSK9 inhibitors has a significant clinical benefit. Increasing evidence that aggressive low-density lipoprotein cholesterol (LDL-C) lowering leads to lower cardiovascular disease risk supports the need for continued exploration of the role of combination lipid-lowering therapies.

Summary

A review of guidelines and clinical trials evaluating non-statin agents illuminates the growing base of evidence and expert opinion supporting the use of combination lipid-lowering therapies. While the majority of clinical trial data utilizes dyslipidemia monotherapy, especially statins, combination therapies represent an opportunity for individualized, patient-centered approach to LDL-C lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction. The overview provides a perspective on lipid management intended for clinicians who seek additional information and guidance on the use of combination therapies.

     

Primary Immunodeficiency Diseases in Latin America: The Second Report of the LAGID Registry

This is the second report on the continuing efforts of LAGID to increase the recognition and registration of patients with primary immunodeficiency diseases in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica, Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report reveals that from a total of 3321 patients registered, the most common form of primary immunodeficiency disease was predominantly antibody deficiency (53.2%) with IgA deficiency reported as the most frequent phenotype. This category was followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune dysregulation, and 2.8% complement deficiencies. All countries that participated in the first publication in 1998 reported an increase in registered primary immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease, and severe combined immunodeficiency between the first report and the present one shows an increase in the reporting of these diseases in all countries. In this report, the estimated minimal incidence of chronic granulomatous disease was between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica, and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and 3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these diseases are underreported in other participating countries. In addition to a better diagnosis of primary immunodeficiency diseases, more work on improving the registration of patients by each participating country and by countries that have not yet joined LAGID is still needed. Latin American Group for Primary Immunodeficiency Diseases